The objective of this project is to identify a humoral satiety factor useful in the treatment of obesity. Three animal models which show evidence of a satiety factor will be evaluated for a humoral substance. These are the satiated rat, jejunoileal intestinal bypass, and transposition of an ileal segment to the jejunum. Preliminary studies have developed a bioassay for rat feeding to test for a humoral satiety factor and techniques of animal surgery necessary for this project. Cross perfusion studies with fed donor rats reveal about a 30% decrease in food consumption in recipient fasted rats compared to controls. Preliminary studies with intestinal bypass suggest an additive effect of obesity on the inhibition of food intake due to bypass. A "dose response" study will be performed to determine the amount of fed rat plasma which must be infused via constant infusion pump to decrease food intake significantly. Similar studies will be carried out in bypass and ileal transposed rats. Cross perfusion studies will be performed in bypass and ileal transposed rats. The effects of leanness vs obesity of the donor rat in inducing satiety will be assessed. Isolation and identification of the humoral substance will be attempted from the plasma and urine of the model having the highest concentration. Column separation, ultramembrane filtration, and dialysis will be performed to assess molecular weight of the substance. Attempts to purify and characterize the substance will be made. More sophisticated biochemical studies will be done in collaboration with other investigators at the University of Virginia who have greater experience in these techniques.